The purpose of this investigation is to examine the structural basis of proline-rich glycoprotein mediated lubrication. The salivary secretions which bathe the oral cavity play a significant role in maintaining the health of the hard and soft tissues of the mouth. This is particularly apparent when one examines patients afflicted with xerostomia. Many of the problems faced by the xerostomic patient may be attributed to a loss of salivary mediated lubrication in the oral cavity, i.e., inadequate slide of masticatory (and/or prosthetic) surfaces in relation to the soft tissues of the mouth leads to difficulty in phonation, mastication and deglutition. Moreover, the absence of a lubricating interface between soft and hard (natural or prosthetic) surfaces of the mouth could increase the incidence of frictional irritation of mucosal surfaces. The mechanisms by which the salivary secretions form a lubrication interface between intercusping teeth and the hard and soft tissues of the oral cavity are poorly understood. However, recent studies have demonstrated that the major glycoprotein of parotid saliva, the proline-rich glycoprotein, displays in vitro lubricating activity. We will examine the structural basis of this activity by assaying defined structural variants of this glycoprotein. These studies may well serve as a prelude for future work, designed to engineer more biologically compatible and efficacious salivary substitutes.